MPOInt: An Epigenetics-Driven Workflow for Integrative Multi-Level Proteomics

Proteomics provides key insights into systems regulating cell behavior and can elucidate key epigenetic states influencing biological functions in health and disease. Integrating different modalities of proteomics (total, phospho, epi) allows for a comprehensive understanding of how systems change in response to a stimulus. A current limitation is that these data are often captured individually with a limited scope of how systems regulating biological processes interact. Integrative analyses are essential to accurately depict biological states but often require custom, time-consuming bioinformatics processing. The MPOInt pipeline and its associated R package provide highly flexible analysis modules that can be easily combined to develop a multidimensional view of the input data with minimal barrier to entry, and is capable of integrating histone proteome data with known epigenetic effectors. Using this tool and pre-existing clinical data, we identify several pathways that may be targets in driving the growth of aggressive cancers, including treatment-resistant estrogen receptor-positive breast cancer. Overall, MPOInt adds clinical context to data that is traditionally difficult to interpret and generates a unique network centered around epigenetic factors for each collection of data.